AUA2021 COURSE: Incorporating Genomic Testing for Prostate Cancer into Your Practice
By: Joseph R. Wagner, MD; Matthew R. Cooperberg, MD; Daniel W. Lin, MD; David F. Penson, MD | Posted on: 06 Dec 2021
At the conclusion of the activity, participants will be able to:
- Describe the seminal validation studies for prostate cancer genomic testing.
- List the different prognostic endpoints provided by various genomic tests.
- Identify appropriate genomic testing based on a patient’s unique clinical characteristics.
- Review the AUA and National Comprehensive Cancer Network® guidelines for genomic testing for prostate cancer.
Mounting evidence suggests genomic tests are useful through all stages of prostate cancer detection and treatment. “Incorporating Genomic Testing for Prostate Cancer into Your Practice” focuses on identifying a patient’s unique clinical characteristics, assessing prognostic end points and reviewing AUA and National Comprehensive Cancer Network® guidelines for genomic testing for prostate cancer.
There are now multiple genomic tests for men at risk for, or diagnosed with, localized prostate cancer which can further risk assess the need for prostate biopsy, aid in making different treatment decisions (active surveillance, surgery, radiation etc), or impact the frequency of cancer monitoring. A patient might migrate away from a prostate biopsy to continued monitoring of his prostate specific antigen and be spared the diagnosis of a clinically insignificant prostate cancer or a complication with a negative biopsy. He may choose active surveillance over definitive therapy based on the result of genomic testing. His genomic test may aid his radiation oncologist concerning the need for concurrent androgen deprivation therapy with his radiation. Genomic testing can help a patient decide whether to pursue adjuvant or early salvage treatment after primary therapy. Clearly, the influence of genomic testing is significant.
The availability and marketing of genomic testing has outpaced a deliberate, evidence-based medicine approach to using these tests. Multiple seminal validation studies used in the approval of genomic tests are reviewed and underscore their importance in prostate cancer detection and treatment decision making. Although not all patients require genomic testing, they can be useful depending on the clinical circumstances.
Before discussing genomic testing, it is important to understand and agree on definitions. Germline tests examine mutations that are inherited from either parent and are present in each cell. Genomic tests examine somatic mutations in the tumor itself. As some tests lumped into this category are not examining mutations (ConfirmMDx®–hypermethylation, ExoDxTM–extracellular vesicle RNA, various protein tests), they are sometimes referred to as molecular tests or assays. A brief biochemistry review showing the path from DNA to RNA to proteins illustrates tests utilize all of these molecules to provide the clinician with critical information.
In determining which patients to test, the first step for doctors should be to familiarize themselves with AUA and National Comprehensive Cancer Network guidelines as well as the genomic tests that are available. All the tests have different clinical end points and utilities; therefore, it is important to understand the characteristics of each to determine which patients are appropriate for genomic testing. It is with this kind of understanding that the doctor and patient can participate in shared decision making.
In the pre-diagnostic setting, our panel feels prostate specific antigen is an excellent biomarker for cancer but can be improved upon with adjunct tests. 4K, PHI, ExoDX, SelectMDx® and PCA3 can all be useful in deciding whether to proceed with a biopsy. These tests, along with ConfirmMDx, can also be helpful in deciding whether to proceed with a second biopsy. Add magnetic resonance imaging to the mix and it is clear the urologist has many tools at his disposal to aid in shared decision making.
Once diagnosed with clinically localized cancer, Prolaris®, Decipher®, OncotypeDX®, and ProMark® can all be used to help determine which patients are more appropriate for active surveillance or definitive therapy. Although all 4 tests have a common goal, all have different, though increasingly overlapping, clinical end points. Prolaris examines the 10-year prostate cancer specific mortality with watchful waiting and the 10-year risk of metastasis after definitive treatment. Decipher reports the 5 and 10-year risk of metastasis after definitive treatment, the 10-year risk of prostate cancer mortality after treatment, and the risk of adverse pathology at surgery. Oncotype utilizes 10-year prostate cancer specific mortality, 10-year risk of metastasis, and adverse pathology, all after surgery. Finally, ProMark examines the risk of adverse pathology at surgery. In addition to categorizing men as appropriate for active surveillance versus treatment, recent studies have demonstrated Decipher can be used to identify patients more apt to benefit from concurrent androgen deprivation therapy with radiation.
In the post-prostatectomy setting, both Decipher (end point metastasis) and Prolaris (end point biochemical recurrence) can help identify men at higher risk for recurrence who may consider earlier adjuvant or salvage treatment. Once again, recent studies have demonstrated Decipher can be used to identify patients more apt to benefit from concurrent androgen deprivation therapy with radiation.
Men with high risk prostate cancer, a family history of germline mutations (BRCA, Lynch etc), Ashkenazi Jewish ancestry, a family history of prostate cancer–first degree (father/brother/son), or multiple Grade Group ≥2/<60 years or who died of prostate cancer, or ≥3 cancers on same side of family (colon, urothelial, breast, pancreas, ovarian)–should consider germline testing. If a germline mutation is discovered, they should be screened appropriately for other cancers for which they are at risk. Family members should be offered genetic counseling to discuss whether they would like to undergo testing. Finally, studies such as PROfound which showed radiographic progression-free survival for patients treated with PARP inhibitors with either BRCA1, BRCA 2, or ATM mutations demonstrate personalized medicine based on mutations is here today.
DNA, RNA and proteins are responsible for the current parameters (prostate specific antigen, Grade Group, etc) used to determine the clinical significance of prostate cancer. It is not surprising that these responsible molecules can be utilized themselves to provide information. Genomic tests are closely entwined with these traditional parameters, making them useful at all stages of prostate cancer treatment. The use of such tests is key for helping urologists stay current in a rapidly changing field.